Early Infant Micronutrition and Development

NCT05005897 | Recruiting Phase 2

• 2 other identifiers: 9305-150426U1111-1267-0112
• Study Type: interventional
• Target: 600
• Locations: 1 country
• Sites: 1

Brief Summary

Globally, vitamin B12 deficiency is one of the most common micronutrient deficiencies. Poor status is also seen in affluent countries such as in Norway. Vitamin B12 is crucial for normal cell division and differentiation and necessary for the development and myelination of the central nervous system. Deficiency is also associated with impaired fetal and infant growth. In the proposed study we will measure the effect of daily oral vitamin B12 supplementation infants on neurodevelopment. We also aim to measure the impact of B12 supplementation on several other outcomes. Study design: Individually randomized double-blind placebo-controlled trial breastfed infants who will be assigned to a screening group (in which measurements will be obtained immediately) or a control group (in which serum will be stored and measurements done after one year). Pregnant women will be informed about the study during their first antenatal visit at the clinic and that we will re-approach them on their 6-week visit to their public health nurse. Infants who are deficient will be treated with peroral or intramuscular injections with 400 µg cyano-cobalamin. Infants in the control group will not be offered any intervention their blood sample will be stored for one year and then analyzed for the same nutrients as the intervention group. Outcomes: Primary: (i) neurodevelopment in children measured at 12 months of age (ii) growth in children measured by attained weight and length at 12 months. Secondary: (i) neurodevelopment and cognitive functioning in children later in life

Conditions

Vitamin B 12 Deficiency

Keywords

Nutrition; Vitamins; Breastfeeding; Infant; Neurodevelopment; Growth; Clinical trial

Outcome Measures

Primary Outcomes (3)

• Neurodevelopment

  Bayley Scales of Infant Development 4th edition

  12 months of age

• Prevalence of vitamin B12 deficiency

  Number of children with elevated plasma homocysteine or low cobalamin

  1-3 months of age

• Prevalence of other vitamin deficiencies

  Number of infants with vitamin deficiencies other than vitamin B12 deficiency

  1-3 months of age

Secondary Outcomes (5)

• Neurodevelopment measured by the Ages and Stages Questionaire

  4-12 months of age

• Vagal tone

  12 months of age

• Eye tracking

  12 months of age

• Neurodevelopment later in childhood

  5 years

• Adverse events

  3 months after treatment with vitamin B12

Other Outcomes (1)

• Thyroid function

  12 months of age

Study Arms (2)

Screening - treatment

EXPERIMENTAL

From 6 weeks of age, infants will be screened for elevated plasma total homocysteine concentrations. Those who have a concentration above the defined cut-off will be treated with cobalamin (vitamin B12).

Biological: Cyanocobalamin

Control

NO INTERVENTION

The control-group sample will be stored and analyzed when the child is 12 months old. Those with elevated tHcy will contribute to the control group.

Interventions

Cyanocobalamin BIOLOGICAL

Intramuscular injection of 400 µg cobalamin to children with elevated thcy at enrollment

Also known as: Vitamin B12

Screening - treatment

Eligibility Criteria

• Age: 1 Month - 2 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Availability of informed verbal consent
• Plan to reside in the defined study area for the next 12 months
• Mothers intend to breastfeed their children for at least 8 months, and exclusively for 4 months

You may not qualify if:

• Severe systemic illness requiring hospitalization
• Growth retardation
• Severe congenital malformations
• Plasma cobalamin concentration \<148 pmol/L (These children will be treated for vitamin B12 deficiency and not included in the RCT, but will be included in the cohort design)

Sponsors & Collaborators

• Sykehuset Innlandet HF: lead
• University of Bergen: collaborator
• University of Oslo: collaborator
• Inland Norway University of Applied Sciences: collaborator

Study Sites (1)

Innlandet Hospital Trust

Lillehammer, 2615, Norway

RECRUITING

Related Publications (10)

• Hay G, Johnston C, Whitelaw A, Trygg K, Refsum H. Folate and cobalamin status in relation to breastfeeding and weaning in healthy infants. Am J Clin Nutr. 2008 Jul;88(1):105-14. doi: 10.1093/ajcn/88.1.105.

  PMID: 18614730 BACKGROUND

• Torsvik I, Ueland PM, Markestad T, Bjorke-Monsen AL. Cobalamin supplementation improves motor development and regurgitations in infants: results from a randomized intervention study. Am J Clin Nutr. 2013 Nov;98(5):1233-40. doi: 10.3945/ajcn.113.061549. Epub 2013 Sep 11.

  PMID: 24025626 BACKGROUND

• Dror DK, Allen LH. Effect of vitamin B12 deficiency on neurodevelopment in infants: current knowledge and possible mechanisms. Nutr Rev. 2008 May;66(5):250-5. doi: 10.1111/j.1753-4887.2008.00031.x.

  PMID: 18454811 BACKGROUND

• Kvestad I, Taneja S, Kumar T, Hysing M, Refsum H, Yajnik CS, Bhandari N, Strand TA; Folate and Vitamin B12 Study Group. Vitamin B12 and Folic Acid Improve Gross Motor and Problem-Solving Skills in Young North Indian Children: A Randomized Placebo-Controlled Trial. PLoS One. 2015 Jun 22;10(6):e0129915. doi: 10.1371/journal.pone.0129915. eCollection 2015.

  PMID: 26098427 BACKGROUND

• Bjorke-Monsen AL. Is exclusive breastfeeding ensuring an optimal micronutrient status and psychomotor development in infants? Clin Biochem. 2014 Jun;47(9):714. doi: 10.1016/j.clinbiochem.2014.05.022. Epub 2014 May 17. No abstract available.

  PMID: 24845709 BACKGROUND

• Forssman L, Ashorn P, Ashorn U, Maleta K, Matchado A, Kortekangas E, Leppanen JM. Eye-tracking-based assessment of cognitive function in low-resource settings. Arch Dis Child. 2017 Apr;102(4):301-302. doi: 10.1136/archdischild-2016-310525. Epub 2016 Aug 22.

  PMID: 27551061 BACKGROUND

• Graziano P, Derefinko K. Cardiac vagal control and children's adaptive functioning: a meta-analysis. Biol Psychol. 2013 Sep;94(1):22-37. doi: 10.1016/j.biopsycho.2013.04.011. Epub 2013 May 4.

  PMID: 23648264 BACKGROUND

• Strand TA, Taneja S, Ueland PM, Refsum H, Bahl R, Schneede J, Sommerfelt H, Bhandari N. Cobalamin and folate status predicts mental development scores in North Indian children 12-18 mo of age. Am J Clin Nutr. 2013 Feb;97(2):310-7. doi: 10.3945/ajcn.111.032268. Epub 2013 Jan 2.

  PMID: 23283502 BACKGROUND

• Bjorkevoll SMG, O'Keeffe M, Konijnenberg C, Solvik BS, Sodal AF, Kaldenbach S, McCann A, Ueland PM, Kvestad I, Ersvaer E, Holten-Andersen MN, Bakken KS, Strand TA. Infant vitamin B12 status and its predictors - cross-sectional baseline results from an ongoing randomized controlled trial. Am J Clin Nutr. 2025 Sep;122(3):803-810. doi: 10.1016/j.ajcnut.2025.06.029. Epub 2025 Jul 1.

  PMID: 40609749 DERIVED

• Bakken KS, Kvestad I, Bjorkevoll SMG, Solvik BS, Kaldenbach S, McCann A, Holten-Andersen MN, Ersvaer E, Konijnenberg C, Strand TA. Vitamin B12 status in infancy and the effect of a vitamin B12 injection in infants with subclinical vitamin B12 deficiency: study protocol for a register-based randomised controlled trial. BMJ Open. 2023 Apr 20;13(4):e069102. doi: 10.1136/bmjopen-2022-069102.

  PMID: 37080624 DERIVED

MeSH Terms

Conditions

Vitamin B 12 Deficiency; Breast Feeding

Interventions

Vitamin B 12

Condition Hierarchy (Ancestors)

Vitamin B Deficiency; Avitaminosis; Deficiency Diseases; Malnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Feeding Behavior; Behavior

Intervention Hierarchy (Ancestors)

Corrinoids; Tetrapyrroles; Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Macrocyclic Compounds; Polycyclic Compounds

Study Officials

• Tor A Strand, M.D. / Ph.D.

  Sykehuset Innlandet HF

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Carolien Konijnenberg, Ph.D

CONTACT

+47 61 28 74 94; carolien.konijnenberg@inn.no

Kjersti S Bakken, Ph.D.

CONTACT

+47 957 81 349; Kjersti.Sletten.Bakken@sykehuset-innlandet.no

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 9, 2021
• First Posted: August 16, 2021
• Study Start: December 8, 2021
• Primary Completion: October 15, 2025
• Study Completion (Estimated): October 15, 2029
• Last Updated: April 18, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data will be available not later than 5 years after the study have completed enrollment and the first year of follow-up of all children.
• Access Criteria: Data available on request. In order to meet ethical requirements for the use of confidential patient data, requests must be approved by Regional Committee for Medical and Health Research Ethics in Norway.

Locations

NO (1)